18F-labeled ethisterone derivative for progesterone receptor targeted PET imaging of breast cancer.

Abstract

PURPOSE:

A novel radiolabeled probe 1‑(17‑[18F]fluoro‑3,6,9,12,15‑pentaoxaheptadecyl‑1H‑1,2,3‑triazole testosterone ([18F]FPTT) was synthesized and evaluated for PET imaging of progesterone receptor (PR)-positive breast cancer.

METHODS:

The ethinyl group of ethisterone, a PR targeting pharmacophore, was coupled with azide modified PEG-OTs by click chemistry to obtain the labeling precursor. The final [18F]FPTT was synthesized by a one-step nucleophilic substitution reaction with 18F. The in vitro stabilities of [18F]FPTT in saline or rat serum were determined after 2 h incubation. Then the in vitro cell binding, ex vivo biodistribution and in vivo imaging of [18F]FPTT were further investigated to evaluate the PR targeting ability and feasibility for the diagnosis of PR-positive breast cancer with PET imaging.

RESULTS:

[18F]FPTT was obtained in high decay-corrected radiochemical yield (78 ± 9%) at the end of synthesis. It had high radiochemical purity (>98%) after HPLC purification and good in vitro stability. The molar activity of [18F]FPTT was calculated as 17 GBq/μmol. The microPET imaging of [18F]FPTT in tumor-bearing mice showed much higher tumor uptake in PR-positive MCF-7 tumor (3.9 ± 0.20%ID/g) than that of PR-negative MDA-MB-231 tumor (1.3 ± 0.08%ID/g). The high MCF-7 tumor uptake could be specifically inhibited by blocking with ethisterone (1.3 ± 0.11%ID/g) or [19F]FPTT (2.20 ± 0.17%ID/g), respectively. The biodistribution in estrogen-primed female SD rats of [18F]FPTT showed high uterus and ovary uptakes (8.31 ± 1.74%ID/g and 3.79 ± 0.82%ID/g at 1 h post-injection). The specific uptakes of uterus and ovary in normal rats were 3.52 ± 0.29%ID/g and 3.22 ± 0.50%ID/g respectively and could be inhibited by co-injecting of ethisterone.

CONCLUSION:

A novel [18F]FPTT probe based on ethisterone modification could be a potential diagnostic agent for PR-positive breast cancer.

• Authors: Fei Gao, Chenyu Peng, Rongqiang Zhuang, Zhide Guo, Huanhuan Liu, Lumei Huang, Hua Li, Duo Xu, Xuejun Wen, Jianyang Fang, Xianzhong Zhang
• Journal: Nuclear medicine and biology (Nucl Med Biol) 2019 May - Jun Vol. 72-73 Pg. 62-69 ISSN: 1872-9614 [Electronic] United States
• PMID: 31330414 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Fluorine Radioisotopes
• Radiopharmaceuticals
• Receptors, Progesterone
• Ethisterone

Topics

• Animals
• Breast Neoplasms (diagnostic imaging, metabolism, pathology)
• Ethisterone (chemistry)
• Female
• Fluorine Radioisotopes (pharmacokinetics)
• Humans
• Mice
• Mice, Inbred BALB C
• Positron-Emission Tomography (methods)
• Radiochemistry
• Radiopharmaceuticals (pharmacokinetics)
• Rats
• Rats, Sprague-Dawley
• Receptors, Progesterone (metabolism)
• Tissue Distribution
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays